Brain communications最新文献

{"title":"Subcortical correlates of sleep in aging and Alzheimer's disease: an <i>in vivo</i> study.","authors":"Agnès Pérez-Millan, Gerard Mayà, Isabel Martín-Sobrino, Marta Peña-González, Andrea Val-Guardiola, Guadalupe Fernández-Villullas, Beatriz Bosch, Adrià Tort-Merino, Albert Lladó, Manuel Morales-Ruiz, Christine M Walsh, Thomas C Neylan, Carles Gaig, Emma Muñoz-Moreno, Raquel Sánchez-Valle, Alex Iranzo, Lea T Grinberg, Neus Falgàs","doi":"10.1093/braincomms/fcag360","DOIUrl":"10.1093/braincomms/fcag360","url":null,"abstract":"<p><p>Sleep disturbances are frequently observed in patients with neurodegenerative diseases, but <i>in vivo</i> evidence linking subcortical sleep-wake structures to sleep phenotypes is limited. We aim to examine associations between MRI-derived measures of subcortical sleep-wake regulating regions and polysomnographic sleep parameters in individuals with Alzheimer's disease and cognitively healthy controls. Fifty-seven adults (45 with biomarker-confirmed Alzheimer's disease and 12 cognitively healthy controls with normal pTau217 plasma levels) were recruited at the Hospital Clínic de Barcelona. All participants completed overnight polysomnography and 3T brain MRI, including a neuromelanin-sensitive sequence. MRI-derived measures of wake-promoting structures [locus coeruleus (LC), posterior hypothalamus and basal forebrain] and sleep-promoting regions (anterior hypothalamus) were obtained. We estimated the association between nocturnal polysomnographic variables [including total sleep time, sleep efficiency, time in rapid eye movement (REM) and non-REM sleep stages, REM sleep latency, wake after sleep onset and arousals] and MRI-derived measures. Then, a principal component analysis (PCA) was used to obtain derived patterns of sleep-wake regulation. Among sleep-promoting regions, higher anterior hypothalamic volumes correlated with greater time in bed (<i>ρ</i> = 0.19, <i>P</i> < 0.05), increased sleep period time (SPT) (<i>ρ</i> = 0.25, <i>P</i> < 0.01), and decreased REM over SPT (<i>ρ</i> = -0.22, <i>P</i> < 0.05). Within wake-promoting structures, higher posterior hypothalamic volume and LC integrity were associated with higher arousals (<i>ρ</i> = 0.32, <i>P</i> < 0.05 and <i>ρ</i> = 0.18, <i>P</i> < 0.05, respectively), and higher basal forebrain volume was associated with less REM over SPT (<i>ρ</i> = -0.25, <i>P</i> < 0.05). Control anatomic regions showed no associations with sleep parameters. The first two principal components of the PCA explain 47.7% of the variance. Anterior hypothalamic volumes clustered with longer, more efficient sleep, whereas LC integrity aligned with increased wakefulness and REM sleep latency. Alzheimer's disease participants showed a shift towards the latter pattern, indicating disrupted sleep-wake regulation. MRI-derived measures of subcortical sleep-wake regions were associated with clinical sleep phenotypes in Alzheimer's disease and ageing. These <i>in vivo</i> findings align with prior post-mortem research, reinforcing the role of subcortical structures in sleep disturbances and highlighting these circuits as potential targets to alleviate sleep symptoms and modify disease progression.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 5","pages":"fcag360"},"PeriodicalIF":4.5,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A cognitive architecture for Long COVID: the interplay of brain fog, fatigue, attention and memory.","authors":"Darragh Higgins, Sijia Zhao, Masud Husain, Peter Denno, Peter J Hellyer, William Trender, Christina J Atchison, Bethan Davies, Emily Cooper, Joshua Elliott, Matthew Whitaker, Chiara Di Gravio, Marc Chadeau-Hyam, Paul Elliott, Helen Ward, Adam Hampshire","doi":"10.1093/braincomms/fcag361","DOIUrl":"10.1093/braincomms/fcag361","url":null,"abstract":"<p><p>The cognitive mechanisms underlying post-acute COVID-19 sequelae ('Long COVID') remain poorly defined. While deficits in memory and executive function are well-documented, it is unclear whether these arise from primary neural dysfunction or are secondary consequences of fatigue-related factors. Here, we addressed this in a community cohort (<i>N</i> = 24 095) using a custom cognitive battery to dissect the interplay between sustained attention, fatigue, and memory. Among this subset, 11 925 participants had previously tested positive for COVID-19, and 548 reported ongoing symptoms consistent with Long COVID. Path analysis (structural equation modelling) was used to evaluate competing mechanistic models linking COVID-19-related features (e.g. duration of symptoms, severity of illness) with objective performance and subjective cognitive symptoms. Participants with persistent symptoms post-COVID-19 (unresolved beyond 12 weeks) showed significant deficits in sustained attention compared to non-infected individuals. Path models revealed complex relationships underlying these deficits. Unlike models of mental health disorders and general ageing, where cognitive performance was largely mediated by relationships to fatigue, the final Long COVID model represented a hybrid mechanism: COVID-19 features were associated with direct, independent effects on attention and memory, while simultaneously relating lower cognitive performance to on-task fatigue build-up. Findings also suggest that 'brain fog' reflects a distinct neurocognitive vulnerability associated with fatigue and reduced performance on sustained attention and memory tasks. These findings accord with the hypothesis that Long COVID has a heterogeneous, multi-faceted impact on cognitive function, with higher-order processes such as memory being particularly vulnerable due to their dependence on foundational attention and motivation processes.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 5","pages":"fcag361"},"PeriodicalIF":4.5,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional reorganization of motor subcircuits in Parkinson's disease.","authors":"Constantina Theofanopoulou, Neha Bajaj, Alberto Muñoz Sánchez, Bruce Crosson, Steven L Wolf, Venkatagiri Krishnamurthy, Keith M McGregor, Madeleine E Hackney","doi":"10.1093/braincomms/fcag354","DOIUrl":"10.1093/braincomms/fcag354","url":null,"abstract":"<p><p>Parkinson's disease disrupts motor control across multiple body parts, yet the neural mechanisms underlying these impairments remain incompletely defined. We compared resting-state functional connectivity in people with mild-to-moderate Parkinson's disease scanned in the OFF-medication state (<i>n</i> = 58) and neurotypical older adults (<i>n</i> = 24), focusing on regions implicated in internally generated and externally generated movement pathways. For our analysis, we leveraged the reproducible NeuroMark independent component template and motor effector-specific mapping of primary motor cortex. Our results reveal both increased and decreased connectivity patterns in Parkinson's disease: primary motor cortex subregions associated with control of the leg, hand, and larynx showed robust increases in connectivity exclusively with cerebellar territories, particularly Crus II and Lobules VIIIa/VIIIb. The postcentral gyrus (primary somatosensory cortex) showed primarily increased connectivity with cerebellar regions and the insula. In contrast, the caudate nucleus displayed a mixed profile, with increased connectivity to the superior temporal gyrus and decreased connectivity to the superior medial frontal gyrus and cerebellar Crus II. A <i>post hoc</i> brain-behaviour analysis further suggested that reduced connectivity between the caudate and superior medial frontal gyrus may be associated with greater overall disease severity. Our motor effector-specific analysis of disease severity scores in people with Parkinson's disease revealed mild impairments across all categories (leg, hand, larynx) but disproportionately greater hand-related deficits, suggesting that some of the observed primary motor cortex connectivity differences may be influenced by these behavioural asymmetries. These anatomically precise, effector-specific alterations suggest compensatory recruitment of cerebellar circuits in Parkinson's disease and provide a framework for targeting motor subcircuits in rehabilitation, including dance-based interventions.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 5","pages":"fcag354"},"PeriodicalIF":4.5,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma cardiac troponin T as a marker of skeletal muscle involvement in amyotrophic lateral sclerosis.","authors":"Linn Öijerstedt, Jianing Lin, Aditya Singh, Solmaz Yazdani, Annamari M Saarinen, Ulf Kläppe, Alexander Juto, Sanharib Chamoun, Sofia Imrell, Fang Fang, Sebastian A Lewandowski, Caroline Ingre","doi":"10.1093/braincomms/fcag358","DOIUrl":"10.1093/braincomms/fcag358","url":null,"abstract":"<p><p>Plasma cardiac troponin T (cTnT) is widely used as a marker of myocardial injury, yet recent studies suggest elevations in amyotrophic lateral sclerosis (ALS). Whether these elevations reflect disease-associated skeletal muscle remodelling remains unresolved. In this translational study, we analysed longitudinal plasma cTnT in a large clinical cohort comprising 496 patients with ALS and 84 with benign fasciculation syndrome (BFS). To investigate the biological origin of circulating cTnT, we examined publicly available skeletal muscle transcriptomes from patients with ALS (<i>n</i> = 28) and healthy controls (<i>n</i> = 17), and quantified troponin isoform expression in skeletal muscle from <i>SOD1^G93A</i> mice and wild-type littermates. Plasma cTnT was significantly higher in ALS than in BFS (median 18 versus 6 ng/L, <i>P</i> = 3.6 × 10^-27), with 57% of patients with ALS exceeding the cardiologic threshold of 15 ng/L. Diagnostic performance was high [area under the curve (AUC) 0.87], with excellent specificity (94%). Longitudinal modelling revealed a progressive increase in cTnT in ALS whereas levels remained stable in BFS. Skeletal muscle transcriptomics demonstrated robust upregulation of <i>TNNT2</i>, encoding cardiac troponin T, in ALS muscle, while other troponin isoforms were unchanged. In <i>SOD1^G93A</i> mice, severely affected gastrocnemius muscle exhibited isoform-specific remodelling, including 20-fold upregulation of <i>Tnnt2</i> and slow-fibre troponins, alongside downregulation of fast skeletal isoforms. Across clinical, transcriptomic, and experimental data, elevated plasma cTnT in ALS is best explained by disease-associated skeletal muscle remodelling rather than cardiomyocyte injury. Plasma cTnT emerges as a dynamic and accessible biomarker in ALS capturing muscle involvement. Prospective incorporation of cTnT into clinical trials and evaluation across broader neuromuscular differentials are warranted.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 5","pages":"fcag358"},"PeriodicalIF":4.5,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The patient-centric development of an inclusive multi-arm multi-stage trial for Parkinson's disease.","authors":"Marie-Louise Zeissler, Matthew Burnell, Thomas R Barber, Yoav Ben-Shlomo, Caroline S Clarke, Sally Collins, Carl Counsell, Joy Duffen, Mark J Edwards, Romy Ellis-Doyle, Cristina Gonzalez-Robles, Kate Hockey, Anna Jewell, Michael Lawton, Georgia Mills, Rebecca Petty, Dorothy Salathiel, Sue Whipps, Alan Whone, Sonia Gandhi, Camille B Carroll, Thomas Foltynie, James R Carpenter, Roger A Barker","doi":"10.1093/braincomms/fcag349","DOIUrl":"10.1093/braincomms/fcag349","url":null,"abstract":"<p><p>There is an urgent need to speed up clinical trials for potential disease-modifying therapies that slow progression of Parkinson's disease. The Edmond J Safra Accelerating Clinical Trials in Parkinson's Disease (EJS ACT-PD) initiative set out to develop a patient-centric and inclusive platform trial using an innovative multi-arm, multi-stage (MAMS) design. We describe the work of the EJS ACT-PD consortium, which included over 90 experts including people with Parkinson's disease and care partners across six working groups. There were five key challenges: developing an efficient MAMS trial that meets regulatory requirements and is acceptable to people with Parkinson's; mitigating participant heterogeneity; reducing the risk of simultaneous arm closures; introducing different treatment regimens into a MAMS trial; and maximizing deliverability and accessibility of a MAMS trial. The final design was achieved through an iterative process and critical appraisal of data modelling exploring the impact of participant numbers per arm, trial durations, and endpoints. Every aspect of the design was informed by people with Parkinson's disease and care partners whose advice ensured acceptability, deliverability, and accessibility. The EJS ACT-PD trial will start with one placebo and three treatment arms, each with 400 participants, with a primary endpoint at 3 years powered to detect a 30% reduction in rate of progression of MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I and II summed scores. Interim analyses will test for activity using the summed inverse variance weighted MDS-UPDRS Part I, II, and remote Part III scores. Ineffective arms will be closed, allowing participants to be re-randomized. Cost-effectiveness analysis is embedded. Further promising treatments will be added in future arms, subject to additional funding. To maximize accessibility and inclusivity, the trial will allow for study visits to be conducted remotely based on participant preference. National sites were selected to maximize accessibility and inclusive recruitment with core funded staff placed within experienced trial sites to support training and delivery at less experienced centres. By involving people with Parkinson's and care partners as well as stakeholders with broad scientific expertise, we have developed an inclusive MAMS trial which captures all stages of disease with partial remote delivery and clear design rationales that will significantly speed up the testing of disease-modifying therapies in Parkinson's disease.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 5","pages":"fcag349"},"PeriodicalIF":4.5,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13616524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced volume of neuromodulatory brainstem nuclei is associated with early hallucination-related vulnerability in Parkinson's disease.","authors":"Gabriella Monopoli, Federica Tomaiuolo, Carlo Sestieri, Miriam Punzi, Simone Marino, Francesco Gambi, Mauro Gianni Perrucci, Antonio Ferretti, Stefano L Sensi, Stefano Delli Pizzi","doi":"10.1093/braincomms/fcag357","DOIUrl":"10.1093/braincomms/fcag357","url":null,"abstract":"<p><p>Early hallucination-related phenomena, including minor visual hallucinations (mVHs), are clinically relevant features of Parkinson's disease (PD), but their neuroanatomical substrates remain unclear. Brainstem nuclei supporting sensory gating, together with cholinergic and noradrenergic dysregulation, are proposed modulators of hallucinations. The objective of the present study was to test whether PD participants with early hallucination-related phenomena show reduced volumes of brainstem nuclei with cholinergic and noradrenergic relevance, using cross-sectional analysis of baseline structural MRI, clinical, and neuropsychological data from 641 PD participants in the Parkinson's Progression Markers Initiative (PPMI). Participants scoring ≥1 at screening, baseline, or during the first nine months of follow-up were categorized as PD-mVHs⁺, whereas those who consistently scored 0 throughout the first year were categorized as PD-mVHs^-. Histology-informed probabilistic atlases were used to segment brainstem, subcortical, and cortical regions. Analyses of covariance (ANCOVAs) compared regional volumes across groups, with group and sex as fixed factors, the group × sex interaction, and age, education, standardized estimated intracranial volume (eTIV), Montreal Cognitive Assessment (MoCA) score, and disease duration as continuous covariates. Hierarchical logistic regression tested whether brainstem volumes added explanatory value for hallucination-related status beyond clinical, neuropsychological, and other volumetric predictors. PD-mVHs⁺ participants showed reduced left locus coeruleus (LC) and left laterodorsal tegmental nucleus (LDTg) volumes, with no significant differences in pedunculopontine tegmental nucleus or dorsal raphe nuclei. After covariate adjustment, the left LDTg effect survived both Bonferroni and false discovery rate (FDR) correction, whereas the left LC effect survived FDR correction but not the Bonferroni-adjusted threshold. Adding LC and LDTg volumes to the hierarchical logistic regression improved fit beyond disease duration, depressive symptoms, immediate verbal recall, and semantic fluency. These findings suggest that reduced MRI-derived volume of the left LDTg, and possibly of the left LC, is associated with early hallucination-related vulnerability in PD.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 5","pages":"fcag357"},"PeriodicalIF":4.5,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149083267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatially convergent functional MRI signatures of diabetes and male sex identify genetic vulnerabilities to accelerated brain ageing.","authors":"Anthony G Chesebro, Luna R Rohm, Botond B Antal, Corey Weistuch, Helmut H Strey, Eva-Maria Ratai, David T Jones, Lilianne R Mujica-Parodi","doi":"10.1093/braincomms/fcag347","DOIUrl":"10.1093/braincomms/fcag347","url":null,"abstract":"<p><p>Age-related cognitive decline results from complex interactions between neuroendocrine and neurometabolic processes that undergo lifelong degradation, yet the mechanisms underlying these interactions remain poorly understood. This study examined the effects of diabetes and sex on functional brain networks across ageing through analysis of two large cohorts (<i>N</i> = 1621 total) using both 3T and 7T functional MRI, complemented by spatial transcriptomic data from over 14 000 genes from six post-mortem brains. Four networks-cingulo-opercular, default mode, salience and lateral somatomotor-exhibited significant functional decline in both individuals with diabetes and independently in males. Gene expression analysis of vulnerable networks revealed significant over-expression of insulin-dependent glucose transporters, dopaminergic and GABAergic synaptic genes and VEGFA-VEGFR2 pathway components. These findings suggest functionally-specific circuit vulnerability to metabolic and hormonal dysregulation, potentially offering targets for early intervention before irreversible neurodegeneration occurs.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 5","pages":"fcag347"},"PeriodicalIF":4.5,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Latent brain-cognition dimension indicative of neuroinflammatory basis of Long COVID.","authors":"Pavel Filip, Eliška Bartečková, Jana Hořínková, Patrik Bartys, David Ulčák, Martin Radvan, Gabriela Matejová, Irena Rektorova, Shalom Michaeli, Silvia Mangia, Lubomír Vojtíšek","doi":"10.1093/braincomms/fcag344","DOIUrl":"10.1093/braincomms/fcag344","url":null,"abstract":"<p><p>Long COVID is characterized by persistent multisystemic symptoms with poorly defined pathophysiological substrate. The presented study investigated whether Long COVID is associated with alterations in brain microstructure and cognition by jointly modelling multimodal MRI and neuropsychological data within a shared framework. One hundred nine participants (77 Long COVID, 32 controls) without the history of severe acute COVID infection underwent quantitative MRI (T₁, T₂, T₁ρ, T₂ρ relaxometry, neurite orientation dispersion and density indices derived from diffusion-weighted imaging) and neuropsychological testing. The resulting brain-cognition axis provided a robust group separation across dimensionalities (permutation <i>P</i> ≈ 0.02), with 72.6% of variance attributable to cognition and 27.4% to MRI features. The predominant imaging features included higher isotropic free-water and reduced neurite density, with minimal relaxometry influence. Projection of discriminant weights back to anatomy revealed involvement over cortico-subcortical dorsal attention, salience and limbic circuits, consistent with patients' cognitive complaints. Furthermore, brain-cognition axis score correlated not only with the global Long COVID symptom burden but also with its respiratory, systemic, and neurological domains without clear predominance for any symptom group (partial <i>R</i> ² ≈ 0.10-0.18, <i>q</i> < 0.01). Hence, although the cognitive profile provided the dominant discriminative anchor in group separation, neuroimaging offered complementary information and pathophysiological background for the clinically apparent cognitive phenotype. The prominence of neuroinflammation-sensitive MRI protocols highlights probable immune and vascular contributions rather than overt neurodegeneration as the basis of Long COVID in individuals without a severe acute infection course.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 5","pages":"fcag344"},"PeriodicalIF":4.5,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network flexibility facilitates treatment-induced recovery in post-stroke aphasia.","authors":"Isaac Falconer, Maria Varkanitsa, Anne Billot, Swathi Kiran","doi":"10.1093/braincomms/fcag279","DOIUrl":"10.1093/braincomms/fcag279","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Predicting the recovery of post-stroke aphasia, particularly in the chronic phase, poses significant challenges. While many studies have focused on static resting state functional connectivity measures as biomarkers for language recovery, there is a significant lack of studies investigating dynamic functional connectivity, which takes into account second to minute timescale variation in connectivity and has been used extensively in other contexts. This retrospective cohort study investigates the predictive value of dynamic functional connectivity for treatment response in post-stroke aphasia. Two temporal metrics, temporal variability and community stability were explored. Temporal variability quantifies the magnitude of variation in the strength of functional connections over time, while community stability measures the mean length of time over which dynamic functional connectivity remains relatively stable. Additionally, a dynamic functional connectivity states analysis, in which time windows are clustered into states using a k-means clustering algorithm, was used to investigate time-varying network properties of dynamic functional connectivity in relation to treatment response. Baseline MRI data were collected for 30 participants with chronic post-stroke aphasia who received a semantic treatment aimed at improving word-finding. Dynamic functional connectivity was generated using a sliding-window approach and the relationships between treatment-induced improvements in naming accuracy and the respective temporal metrics and network properties were evaluated using linear mixed effects models predicting naming accuracy. Specifically, a significant interaction effect of session (i.e. time) and the respective measure was interpreted as a significant relationship between the measure and treatment response. Both temporal metrics were found to be significantly associated with naming improvements, with both higher temporal variability (i.e. magnitude of fluctuations in dynamic functional connectivity; interaction effect: &lt;i&gt;β&lt;/i&gt; = 0.45, &lt;i&gt;P&lt;/i&gt; = 3.6e-09, &lt;i&gt;η&lt;/i&gt;1 = 0.072) and higher community stability (i.e. moment-to-moment stability of dynamic functional connectivity; interaction effect: &lt;i&gt;β&lt;/i&gt; = 0.0046, &lt;i&gt;P&lt;/i&gt; = 5.4e-06, &lt;i&gt;η&lt;/i&gt; &lt;sup&gt;1&lt;/sup&gt; = 0.044) predicting greater treatment gains. These findings suggest that patients who benefit most from treatment have neural dynamics characterized by a large magnitude, but low frequency, of fluctuations in network synchrony. Finally, consistent with previous studies, patients who spent more time in a state characterized by higher modularity showed greater treatment response (interaction effect: &lt;i&gt;β&lt;/i&gt; = 7.9e-05, &lt;i&gt;P&lt;/i&gt; = 6.2e-04, &lt;i&gt;η&lt;/i&gt; &lt;sup&gt;1&lt;/sup&gt; = 0.025). Overall, the findings of this study provide evidence for the utility of dynamic functional connectivity in studying post-stroke language recovery as a measure that captures interindividual difference in the capacity for recovery. They","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 5","pages":"fcag279"},"PeriodicalIF":4.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149009595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic alterations in the absence of a neuromuscular phenotype in humanized <i>SOD1^A5V</i> mice.","authors":"David Thompson, Chloe Williams, Georgia Price, Andrew P Tosolini, Clemens Falker-Gieske, Jonathan D Gilthorpe, Giampietro Schiavo, Elizabeth M C Fisher, Thomas J Cunningham","doi":"10.1093/braincomms/fcag302","DOIUrl":"10.1093/braincomms/fcag302","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis caused by mutations in <i>superoxide dismutase 1</i> (<i>SOD1</i>) accounts for 15-30% of familial cases and is typically autosomal dominant. How single amino acid changes in this small protein cause neurodegeneration is unknown. In North America, <i>SOD1^A5V</i> is the most common familial <i>SOD1</i> mutation and results in an aggressive form of amyotrophic lateral sclerosis. Here, we present a novel genomically humanized mouse model of <i>SOD1^A5V</i> , in which the mouse <i>Sod1</i> locus has been replaced by the human <i>SOD1</i> gene, with intact genomic architecture of exons and introns, but bearing an A5 V mutation. In agreement with previously reported human genomic knock-in mice, the phenotype is mild; however, transcriptomic and metabolomic profiling reveal significant dysregulation of glycolysis, the tricarboxylic acid cycle, and lipid metabolism. These changes suggest an early bioenergetic imbalance that precedes neuromuscular impairment. Our findings support metabolic dysfunction as an early event in amyotrophic lateral sclerosis pathogenesis. This freely available <i>SOD1^A5V</i> model provides a valuable tool for studying amyotrophic lateral sclerosis progression and identifying therapeutic targets for pre-symptomatic treatment.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 5","pages":"fcag302"},"PeriodicalIF":4.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13583902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148993107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}